Hyaluronic acid (HA) is a polysaccharide that is present within the extracellular matrix (ECM) of many[unreadable] connective tissues, including tendon. Recent studies have revealed an active role for HA during wound[unreadable] healing, whereby it induces inflammatory gene expression through direct interaction with cell surface[unreadable] receptors. The overall aim of this bioengineering study is to examine the effect of HA/receptor interaction in[unreadable] healing tendon and to determine the role of key mediators in this process. The overall hypothesis is that[unreadable] HA/receptor interactions, primarily those mediated by its cell associated receptors CD44 and RHAMM, are[unreadable] critical for initiation and regulation of the inflammatory cascade that characterizes adult tendon healing, and[unreadable] for the fibrosis that ensues. Our specific aims and hypotheses are: Specific Aim 1: To analyze the effects of[unreadable] globally inhibiting HA/receptor interactions in injured patellar tendons by evaluating the inflammatory cytokine[unreadable] response and mechanical properties of the injured tissue. Hypothesis 1A: Tendons of mice treated with a[unreadable] peptide that competitively inhibits HA/receptor interactions will exhibit decreased expression of proinflammatory[unreadable] cytokines one and three days post-injury. Hypothesis 1B: Tendons of mice treated with a[unreadable] peptide that competitively inhibits HA/receptor interactions will exhibit superior mechanical properties three[unreadable] and six weeks post-injury. Specific Aim 2: To analyze the effects of CD44 deficiency in injured patellar[unreadable] tendons by evaluating the inflammatory cytokine response and mechanical properties of the injured tissue.[unreadable] Hypothesis 2A: Tendons of CD44 knockout mice will exhibit decreased expression of pro-inflammatory[unreadable] cytokines one and three days post-injury. Hypothesis 2B: Tendons of CD44 knockout mice will exhibit[unreadable] inferior mechanical properties three and six weeks post-injury. Specific Aim 3: To analyze the effects of[unreadable] RHAMM deficiency in injured patellar tendons by evaluating the inflammatory cytokine response and[unreadable] mechanical properties of the injured tissue. Hypothesis 3A: Tendons of RHAMM knockout mice will exhibit[unreadable] decreased expression of pro-inflammatory cytokines one and three days post-injury. Hypothesis 3B:[unreadable] Tendons of RHAMM knockout mice will exhibit superior mechanical properties three and six weeks postinjury.[unreadable] Although a great deal of insight has been gained into HA and its receptors with regard to their roles in[unreadable] inflammation, little is known about their involvement in tendon healing. If successful, this study will better[unreadable] define the functions of two important HA receptors and help to determine the effect of HA/receptor interaction[unreadable] on tendon wound healing. This information will present exciting avenues for the development of novel,[unreadable] clinical applications and thus lead to immensely beneficial improvements in the treatment of tendon injuries.[unreadable]